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1.
Eur J Med Chem ; 264: 115953, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38029466

RESUMO

Tropomyosin receptor kinase (TRK) is a promising target for treating NTRK fusion cancers. The solvent front and xDFG mutations induced by larotrectinib and entrectinib result in acquired resistance in advanced-stage patients. In this study, we report a highly potent and selective type II TRK inhibitor, 40l, developed using a structure-based design strategy. Compound 40l significantly suppressed Km-12, Ba/F3-TRKAG595R, and Ba/F3-TRKAG667C cell proliferation. In biochemical and cellular assays, 40l showed better inhibitory activity against TRKAG667C than that by the positive control, selitrectinib. Additionally, it induced apoptosis of Ba/F3-TRKAG595R and Ba/F3-TRKAG667C cells in a dose-dependent manner. Furthermore, 40l showed good selectivity for a panel of 41 kinases. In vitro assays indicated that 40l possessed outstanding plasma stability and moderate liver microsomal stability. Based on the above results, compound 40l could be further optimized to overcome the solvent front and xDFG TRK mutations.


Assuntos
Neoplasias , Receptor trkA , Humanos , Neoplasias/genética , Indazóis/farmacologia , Solventes , Inibidores de Proteínas Quinases/farmacologia
2.
Int J Mol Sci ; 24(14)2023 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-37511349

RESUMO

Cadmium (Cd) contamination in rice grains is posing a significant threat to global food security. To restrict the transport of Cd in the soil-rice system, an efficient way is to use the ionomics strategy. Since calcium (Ca) and Cd have similar ionic radii, their uptake and translocation may be linked in multiple aspects in rice. However, the underlying antagonistic mechanisms are still not fully understood. Therefore, we first summarized the current knowledge on the physiological and molecular footprints of Cd translocation in plants and then explored the potential antagonistic points between Ca and Cd in rice, including exchange adsorption on roots, plant cell-wall composition, co-transporter gene expression, and transpiration inhibition. This review provides suggestions for Ca/Cd interaction studies on rice and introduces ionomics research as a means of better controlling the accumulation of Cd in plants.


Assuntos
Oryza , Poluentes do Solo , Cádmio/metabolismo , Cálcio/metabolismo , Oryza/genética , Oryza/metabolismo , Transporte Biológico , Solo , Cálcio da Dieta/metabolismo , Poluentes do Solo/metabolismo , Raízes de Plantas/metabolismo
3.
Quant Imaging Med Surg ; 13(4): 2441-2450, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37064358

RESUMO

Background: There were no effective noninvasive methods to diagnose renal ischemia-reperfusion injury (IRI), which is a major clinical problem. The objective of this study was to explore the feasibility of the quantitative susceptibility mapping (QSM) technique in evaluating the dynamic changes in the renal IRI process. Methods: A total of 36 New Zealand rabbits were randomly assigned to the IRI group (n=30) and the sham group (n=6). All rabbits underwent magnetic resonance imaging (MRI) examination, including T2-weighted imaging and QSM before the operation (pre-IRI) and 1, 12, 24, and 48 h after the operation (IRI-1h, IRI-12h, IRI-24h, and IRI-48h, respectively). Regions of interest were manually delineated in the outer medulla. All specimens were stained with hematoxylin and eosin (HE) and glutathione peroxidase 4 (GPX4). The pathological score of renal injury and the average optical density value of GPX4 were calculated. The repeated measurement analysis of variance (ANOVA) and Spearman correlation analysis were used to compare the differences between the susceptibility values and determine the correlation. Results: In the IRI group, the susceptibility values of the outer medulla at the pre-IRI, IRI-1h, IRI-12h, IRI-24h, and IRI-48h time points were (42.83±7.83)×10-3, (-5.33±6.28)×10-3, (6.50±3.94)×10-3, (12.00±3.74)×10-3, and (22.00±6.81)×10-3 ppm, respectively. The susceptibility values significantly differed among the different time points (P<0.001). The susceptibility values had a negative correlation with the scores of cell edema (ρ=-0.61; P=0.002) and the average optical density value of GPX4 (ρ=-0.70; P<0.001). The susceptibility values had a positive correlation with iron content (ρ=0.79; P<0.001), the scores of cell necrosis (ρ=0.71; P<0.001), interstitial inflammation (ρ=0.60; P=0.002), cast (ρ=0.75; P<0.001), and the total pathological score of renal injury (ρ=0.51; P=0.01). Conclusions: QSM can be used as a noninvasive method to assess the dynamic changes of the outer medulla in the early stage of renal IRI in rabbits.

4.
Eur J Med Chem ; 253: 115291, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-37030091

RESUMO

Tropomyosin receptor kinases (TRKs) are effective targets for anti-cancer drug discovery. The first-generation type I TRKs inhibitors, larotrectinib and entrectinib, exhibit durable disease control in the clinic. The emergence of acquired resistance mediated by secondary mutations in the TRKs domain significantly reduces the therapeutic efficacy of these two drugs, indicating an unmet clinical need. In this study, we designed a potent and orally bioavailable TRK inhibitor, compound 24b, using a molecular hybridization strategy. Compound 24b exhibited significant inhibitory potency against multiple TRK mutants in both biochemical and cellular assays. Furthermore, compound 24b induced apoptosis of Ba/F3-TRKAG595R and Ba/F3-TRKAG667C cells in a dose-dependent manner. Additionally, compound 24b exhibited moderate kinase selectivity. In vitro stability revealed that compound 24b showed excellent plasma stability (t1/2 > 289.1 min) and moderate liver microsomal stability (t1/2 = 44.3 min). Pharmacokinetic studies have revealed that compound 24b is an orally bioavailable TRK inhibitor with a good oral bioavailability of 116.07%. These results indicate that compound 24b be used as a lead molecule for further modifications to overcome drug-resistant mutants of TRK.


Assuntos
Antineoplásicos , Neoplasias , Humanos , Receptor trkA , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Indóis/farmacologia , Indóis/uso terapêutico , Inibidores de Proteínas Quinases/química
5.
RSC Med Chem ; 14(1): 85-102, 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36760745

RESUMO

Tropomyosin receptor kinases (TRKs) are associated with the proliferation and differentiation of cells, and thus their continuous activation and overexpression cause cancer. Herein, based on scaffold hopping and computer-aid drug design, 38 pyrazolo[3,4-b]pyridine derivatives were synthesised. Further, we evaluated their activities to inhibit TRKA. Among them, compound C03 showed acceptable activity with an IC50 value of 56 nM and it inhibited the proliferation of the Km-12 cell line with an IC50 value of 0.304 µM together with obvious selectivity for the MCF-7 cell line and HUVEC cell line. Furthermore, compound C03 possessed good plasma stability and low inhibitory activity to a panel of cytochrome P450 isoforms except CYP2C9. Overall, C03 has potential for further exploration.

6.
Chemosphere ; 311(Pt 1): 137073, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36332733

RESUMO

Runoff loss of nitrogen from paddy fields has received increasing attention in recent years. Duckweed is an aquatic plant frequently found in paddy fields. In this study, the effects of duckweed (Lemna minor L.) in floodwater on aqueous nitrogen losses from paddy fields were systematically investigated. Results demonstrated that the growth of duckweed decreased total nitrogen concentrations in floodwater and nitrogen runoff loss from paddy fields by 16.7%-18.3% and 11.2%-13.6%, respectively. Moreover, compared with NO3-, NH4+ was preferentially removed by duckweed. 15N isotope tracer experiments revealed that the growth and decomposition of duckweed acted as a "buffer" against the nitrogen variation in floodwater after fertilization. During the growth of duckweed, leaves were found to be the principal organ to assimilate NH4+ and release NO3- by using non-invasive micro-test technology. Duckweed degradation increased the content of hydrophobic acids and marine humic-like substances in floodwater, which promoted the migration of nitrogen from floodwater to soil. Redundancy analysis and structural equation models further illustrated that pH and temperature variation in floodwater caused by duckweed played a greater role in aqueous nitrogen loss reduction than the nitrogen accumulation in duckweed. This study suggested that the growth of duckweed in paddy fields was an effective supplementary method for controlling aqueous nitrogen loss during agricultural production.


Assuntos
Araceae , Oryza , Nitrogênio/análise , Fertilizantes/análise , Oryza/metabolismo , Agricultura/métodos , Araceae/metabolismo , Água/química , Fertilização
7.
Biology (Basel) ; 11(8)2022 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-36009760

RESUMO

Intercropping plants for phytoremediation is a promising strategy in heavy metal-polluted soils. In this study, two typical greening plant species, Euonymus japonicus (E. japonicus) and Photinia × fraseri (P. × fraseri), were intercropped in a Cd/Cu/Zn-contaminated field. The phytoremediation efficiency was investigated by measuring the plant biomass, metal concentration, and mycorrhizal colonisation, as well as the effects on soil properties, including soil pH; soil total N; and available N, P, K, Cd, Cu, and Zn. The results showed that, compared with the monoculture system, intercropping significantly lowered the available Cd, Cu, and Zn contents, significantly improved the total and available N contents in rhizosphere soils of both plant species, and increased the hyphae colonisation rate of P. × fraseri. In both plants, intercropping significantly improved the total plant biomass. Furthermore, the concentrations Zn and Cd in the root of E. japonicus and Cu concentration in the root of P. × fraseri were enhanced by 58.16%, 107.74%, and 20.57%, respectively. Intercropping resulted in plants accumulating higher amounts of Cd, Cu, and Zn. This was particularly evident in the total amount of Cd in E. japonicus, which was 2.2 times greater than that in the monoculture system. Therefore, this study provides a feasible technique for improving phytoremediation efficiency using greening plants.

8.
J Enzyme Inhib Med Chem ; 37(1): 2241-2255, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35978496

RESUMO

FAK mediated tumour cell migration, invasion, survival, proliferation and regulation of tumour stem cells through its kinase-dependent enzymatic functions and kinase-independent scaffolding functions. At present, the development of FAK PROTACs has become one of the hotspots in current pharmaceutical research to solve above problems. Herein, we designed and synthesised a series of FAK-targeting PROTACs consisted of PF-562271 derivative 1 and Pomalidomide. All compounds showed significant in vitro FAK kinase inhibitory activity, the IC50 value of the optimised PROTAC A13 was 26.4 nM. Further, A13 exhibited optimal protein degradation (85% degradation at 10 nM). Meantime, compared with PF-562271, PROTAC A13 exhibited better antiproliferative activity and anti-invasion ability in A549 cells. More, A13 had excellent plasma stability with T1/2 >194.8 min. There are various signs that PROTAC A13 could be useful as expand tool for studying functions of FAK in biological system and as potential therapeutic agents.


Assuntos
Antineoplásicos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Fosforilação , Proteólise
9.
Life (Basel) ; 12(6)2022 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-35743917

RESUMO

In recent decades, many new and exciting findings have paved the way to the better understanding of plant responses in various environmental changes. Some major areas are focused on role of phytohormone during abiotic stresses. Salicylic acid (SA) is one such plant hormone that has been implicated in processes not limited to plant growth, development, and responses to environmental stress. This review summarizes the various roles and functions of SA in mitigating abiotic stresses to plants, including heating, chilling, salinity, metal toxicity, drought, ultraviolet radiation, etc. Consistent with its critical roles in plant abiotic tolerance, this review identifies the gaps in the literature with regard to the complex signalling network between SA and reactive oxygen species, ABA, Ca2+, and nitric oxide. Furthermore, the molecular mechanisms underlying signalling networks that control development and stress responses in plants and underscore prospects for future research on SA concerning abiotic-stressed plants are also discussed.

10.
Sheng Wu Gong Cheng Xue Bao ; 38(1): 287-302, 2022 Jan 25.
Artigo em Chinês | MEDLINE | ID: mdl-35142138

RESUMO

As a non-essential metal, cadmium (Cd) pollution poses severe threats to plant growth, environment, and human health. Phytoextraction using nursery stocks prior to their transplantation is a potential useful approach for bioremediation of Cd contaminated soil. A greenhouse pot experiment was performed to investigate the growth, Cd accumulation, profiles of transcriptome as well as root-associated microbiomes of Photinia frase in Cd-added soil, upon inoculation of two types of arbuscular mycorrhizal fungi (AMF) Sieverdingia tortuosa and Funneliformis mosseae. Compared with the control, inoculation of F. mosseae increased Cd concentrations in root, stem and leaf by 57.2%, 44.1% and 71.1%, respectively, contributing to a total Cd content of 182 µg/plant. KEGG pathway analysis revealed that hundreds of genes involved in 'Mitogen-activated protein kinase (MAPK) signaling pathway', 'plant hormone signal transduction', 'biosynthesis of secondary metabolites' and 'glycolysis/gluconeogenesis' were enriched upon inoculation of F. mosseae. The relative abundance of Acidobacteria was increased upon inoculation of S. tortuosa, while Chloroflexi and Patescibacteria were increased upon inoculation of F. mosseae, and the abundance of Glomerales increased from 23.0% to above 70%. Correlation analysis indicated that ethylene-responsive transcription factor, alpha-aminoadipic semialdehyde synthase, isoamylase and agmatine deiminase related genes were negatively associated with the relative abundance of Glomerales operational taxonomic units (OTUs) upon inoculation of F. mosseae. In addition, plant cysteine oxidase, heat shock protein, cinnamoyl-CoA reductase and abscisic acid receptor related genes were positively associated with the relative abundance of Patescibacteria OTUs upon inoculation of F. mosseae. These finding suggested that AMF can enhance P. frase Cd uptake by modulating plant gene expression and altering the structure of the soil microbial community. This study provides a theoretical basis for better understanding the relationship between root-associated microbiomes and root transcriptomes of P. frase, from which a cost-effective and environment-friendly strategy for phytoextraction of Cd in Cd-polluted soil might be developed.


Assuntos
Microbiota , Micorrizas , Photinia , Poluentes do Solo , Cádmio , Humanos , Transcriptoma
11.
Environ Pollut ; 280: 116996, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33784563

RESUMO

A key challenge for phytoextraction is the identification of high efficiency, growth-supporting, and low cost chelating agents. To date, no substance has satisfied all above criteria. This study investigated nine traditional Chinese herbs and found that Phyllanthus emblica fruit (FPE) extract could be utilised as an optimal chelate for the phytoextraction of cadmium (Cd)-contaminated soils. FPE application into soil at a ratio of 0.1% (w/w) significantly increased extractable Cd (by 43%) compared to the control. The success of FPE as a chelating agent was attributed to high quantities of polyphenol compounds (0.76%) and organic acids (9.6%), in particular, gallic acid (7.6%). Furthermore, antioxidative properties (1.4%) and free amino acids in FPE alleviated Cd-induced oxidant toxicity and enhanced plant biomass. FPE promoted 78% higher phytoextraction efficiency in Platycladus orientalis compared to traditional chelating agents (EDTA). Furthermore, 76% of FPE was degraded 90 days after the initial application, and there was no difference in extractable Cd between the treatment and control. FPE has been commercially produced at a lower market price than other biodegradable chelates. As a commercially available and cost-effective chelator, FPE could be utilised to treat Cd-contaminated soils without adverse environmental impacts.


Assuntos
Phyllanthus emblica , Poluentes do Solo , Animais , Biodegradação Ambiental , Cádmio/análise , Quelantes , Ácido Edético , Frutas/química , Extratos Vegetais , Solo , Poluentes do Solo/análise
12.
Sci Rep ; 11(1): 6325, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737581

RESUMO

Cadmium (Cd) presents severe risks to human health and environments. The present study proposed a green option to reduce bioavailable Cd. Rice pot experiments were conducted under continuous flooding with three treatments (T1: intercropping azolla with rice; T2: incorporating azolla into soil before rice transplantation; CK: no azolla). The results showed that azolla incorporation reduced soluble Cd by 37% compared with the CK treatment, which may be explained by the decreased soil redox potential (Eh) (r = 0.867, P < 0.01). The higher relative abundance of Methylobacter observed in azolla incorporation treatment may account for dissolved organic carbon increase (r = 0.694; P < 0.05), and hence decreased the Cd availability for rice. Azolla incorporation increased the abundance of Nitrospira, indicating the potentially prominent role of nitrogen mineralization in increasing rice yields. Further, lower soluble Cd decreased the expression of OsNramp5, but increased OsHMA3 levels in rice roots, which decreased Cd accumulation in grains. Through these effects, azolla incorporation decreased Cd concentrations in rice grains by 80.3% and increased the production by 13.4%. The negligible amount of Cd absorbed by azolla would not increase the risk of long-term application. Thus, intercropping azolla with early rice and incorporating azolla into soil before late rice transplantation can contribute to safe production at large scales of double rice cultivation.

13.
Sci Rep ; 10(1): 11490, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32661359

RESUMO

A regional field survey of a total of 109 pairs of soil and rice samples was conducted to evaluate the health risks posed by heavy metals in the Jin-Qu Basin, China. The studied soils are characterized by acid (pH in mean level of 5.5), carbon rich (soil organic matter in mean of 33.6 g kg-1) and mainly contaminated by Cd (42.2% samples exceeded the standard value of 0.3 mg kg-1 (GB15618-2018)). The spatial distributions of Cd, Pb and Zn exhibited similar geographic trends. 34% and 30% of the rice samples containing Cd and Pb exceeded the threshold value of 0.2 mg kg-1 (GB2762-2017), respectively. The risk estimation of dietary intake had a target hazard quotient value of Cd of 0.918 and a hazard index value for rice consumption of 2.141. Totally, Cd and Pb were found to be the main components contributing to the potential health risks posed by non-carcinogenic effects for local inhabitants.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/toxicidade , Medição de Risco , Poluentes do Solo/toxicidade , China/epidemiologia , Poluição Ambiental/prevenção & controle , Humanos , Oryza/efeitos dos fármacos , Oryza/crescimento & desenvolvimento , Solo/química
14.
Int J Mol Sci ; 20(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216620

RESUMO

Salicylic acid (SA), as an enigmatic signalling molecule in plants, has been intensively studied to elucidate its role in defence against biotic and abiotic stresses. This review focuses on recent research on the role of the SA signalling pathway in regulating cadmium (Cd) tolerance in plants under various SA exposure methods, including pre-soaking, hydroponic exposure, and spraying. Pretreatment with appropriate levels of SA showed a mitigating effect on Cd damage, whereas an excessive dose of exogenous SA aggravated the toxic effects of Cd. SA signalling mechanisms are mainly associated with modification of reactive oxygen species (ROS) levels in plant tissues. Then, ROS, as second messengers, regulate a series of physiological and genetic adaptive responses, including remodelling cell wall construction, balancing the uptake of Cd and other ions, refining the antioxidant defence system, and regulating photosynthesis, glutathione synthesis and senescence. These findings together elucidate the expanding role of SA in phytotoxicology.


Assuntos
Cádmio/toxicidade , Resistência à Doença , Doenças das Plantas/etiologia , Plantas/efeitos dos fármacos , Plantas/metabolismo , Ácido Salicílico/metabolismo , Transdução de Sinais , Adaptação Biológica , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Cádmio/metabolismo , Fotossíntese/efeitos dos fármacos , Doenças das Plantas/prevenção & controle , Espécies Reativas de Oxigênio/metabolismo , Ácido Salicílico/farmacologia , Estresse Fisiológico
15.
PLoS One ; 14(1): e0210614, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30682059

RESUMO

Four methods, including hot acid treatment, hot alkali treatment, calcination treatment and sulfhydrylation treatment, were applied to activate alum plasma in order to obtain new Pb2+ adsorbents. The corresponding adsorption isotherm satisfies the Langmuir equation, and the maximum adsorption of the alum plasma after hot acid treatment, hot alkali treatment and high-temperature calcination were 18.9, 57.3 and 10.9 mg·g-1, respectively, and in the range of 1.23-6.57 times greater than the adsorption capacity of the original alum plasma. The soil culture experiments indicated that the effective Pb content in the soils treated with hot alkali ameliorated alum plasma was significantly lower (p < 0.05) than those treated with the other three types of alum plasma. For example, if the additive content is 5.0%, after a storage period of 16 weeks, the effective Pb content becomes 19.87 mg·kg-1, which corresponds to a reduction of 60.9% in comparison with the control sample. In addition, Specific surface area (BET), Scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FIR) were used to characterize the microstructure of alum plasma before and after amelioration. It was evident that hot alkali treatment of alum plasma resulted in smaller particles, a significantly higher specific area and lower mineral crystallinity, which improved the adsorption performance of Pb2+. In conclusion, hot alkali treatment of alum plasma indicates relatively good Pb2+ adsorption ability, and is a promising novel adsorbents that could ameliorate soils that have been polluted by heavy metal Pb.


Assuntos
Compostos de Alúmen/química , Chumbo/química , Poluentes do Solo/química , Poluentes da Água/química , Ácidos/química , Adsorção , Algoritmos , Álcalis/química , Poluição Ambiental/análise , Poluição Ambiental/prevenção & controle , Temperatura Alta , Cinética , Microscopia Eletrônica de Varredura , Modelos Químicos , Tamanho da Partícula
16.
J Hazard Mater ; 316: 77-86, 2016 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-27209521

RESUMO

A few studies with NahG transgenic lines of Arabidopsis show that depletion of SA enhances cadmium (Cd) tolerance. However, it remains some uncertainties that the defence signaling may be a result of catechol accumulation in NahG transgenic lines but not SA deficiency. Here, we conducted a set of hydroponic assays with another SA-deficient mutant sid2 to examine the endogenous roles of SA in Cd tolerance, especially focusing on the glutathione (GSH) cycling. Our results showed that reduced SA resulted in negative effects on Cd tolerance, including decreased Fe uptake and chlorophyll concentration, aggravation of oxidative damage and growth inhibition. Cd exposure significantly increased SA concentration in wild-type leaves, but did not affect it in sid2 mutants. Depletion of SA did not disturb the Cd uptake in either roots or shoots. The reduced Cd tolerance in sid2 mutants is due to the lowered GSH status, which is associated with the decreased expression of serine acetyltransferase along with a decline in contents of non-protein thiols, phytochelatins, and the lowered transcription and activities of glutathione reductase1 (GR1) which reduced GSH regeneration. Finally, the possible mode of SA signaling through the GR/GSH pathway during Cd exposure is discussed.


Assuntos
Arabidopsis/genética , Arabidopsis/metabolismo , Cádmio/química , Glutationa/metabolismo , Ácido Salicílico/química , Antioxidantes/química , Arabidopsis/efeitos dos fármacos , Catecóis/química , Hidroponia , Mutação , Oxirredução , Estresse Oxidativo , Fitoquelatinas/metabolismo , Folhas de Planta/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/efeitos dos fármacos
17.
J Environ Manage ; 134: 39-46, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-24463847

RESUMO

The aim of this study was to propose a feasible treatment of kitasamycin manufacturing waste by examining extractable kitasamycin and evaluating its compost maturity during the composting of waste with different ratios of dairy manure and sawdust over a 40-day period (volume/volume/volume; M1, 0/80/20; M2, 10/70/20; and M3, 30/50/20). During composting, the concentration of extractable kitasamycin in kitasamycin-contaminated composts declined rapidly, and was undetectable in M2 within 15 days. M2 also achieved the highest fertility compost, which was characterised by the following final parameters: electrical conductivity, 2.34 dS cm(-1); pH, 8.15; total C/N, 22.2; water-soluble NH4(+), P, and K, 0.37, 3.43, and 1.05 g kg(-1), respectively; and plant germination index values, 92%. Furthermore, DGGE analysis showed a dramatic increase in the diversity of bacterial species during composting. In contrast, a high concentration (121 mg kg(-1)) of extractable kitasamycin still remained in the M3 compost, which exerted an inhibitory effect on the composting, resulting in reduced bacterial diversity, high values of electrical conductivity and water-soluble NH4(+), a low C/N ratio, and a low plant germination index value. Furthermore, 3.86 log (CFU g(-1)) kitasamycin-resistant bacteria were still present on day 40, indicating the biological degradation contributed to the decline of extractable kitasamycin.


Assuntos
Antibacterianos/análise , Resíduos Industriais/análise , Kitasamicina/análise , Esterco , Gerenciamento de Resíduos/métodos , Madeira , Indústria de Laticínios , Solo/química , Microbiologia do Solo
18.
J Mol Med (Berl) ; 91(1): 37-47, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22772377

RESUMO

Excessive activation of the transforming growth factor beta signaling pathway and disorganized cellular skeleton caused by genetic mutations are known to be responsible for the inherited thoracic aortic aneurysms and dissections (TAAD), a life-threatening vascular disease. To investigate the genotype-phenotype correlation, we screened genetic mutations of fibrillin-1 (FBN1), transforming growth factor-ß receptor-1 (TGFBR1) and transforming growth factor-ß receptor-2 (TGFBR2) for TAAD in 7 affected families and 22 sporadic patients. Of 19 potential mutations identified in FBN1, 11 appeared novel while the others were recurrent. Two mutations were detected in TGFBR2. Eight patients carried no mutation in either of these genes. Characterization of FBN1 c.5917+6T>C in transfected HEK293 cells demonstrated that it caused skipping of exon 47, leading to the loss of the 33th calcium binding epidermal growth factor-like domain associated with Marfan syndrome. Compared with exon 46, skipping of 47 did not cause patients ectopia lentis in all carriers. To correlate genotypes with phenotypes in different human ancestries, we reviewed the published mutational studies on FBN1 and found that the probability of cardiovascular defects were significantly increased in Chinese patients with premature termination codon or splicing mutations than those with missense mutations (91.7 % vs 54.2 %, P = 0.0307) or with noncysteine-involved point mutations than those with cysteine-involved mutations (88.9 % vs 33.3 %, P = 0.0131). Thus, we conclude that exon 47 skipping of FBN1 leads preferentially to cardiovascular defects and human ancestries influence genotype-phenotype correlation in TAAD.


Assuntos
Aorta Torácica/metabolismo , Aneurisma da Aorta Torácica/genética , Dissecção Aórtica/genética , Proteínas dos Microfilamentos/genética , Adolescente , Adulto , Dissecção Aórtica/etnologia , Dissecção Aórtica/patologia , Aorta Torácica/patologia , Aneurisma da Aorta Torácica/etnologia , Aneurisma da Aorta Torácica/patologia , Povo Asiático , Criança , Éxons , Feminino , Fibrilina-1 , Fibrilinas , Expressão Gênica , Estudos de Associação Genética , Células HEK293 , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Linhagem , Proteínas Serina-Treonina Quinases/genética , Estrutura Terciária de Proteína , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética , Transfecção
19.
Zhonghua Xin Xue Guan Bing Za Zhi ; 40(2): 104-7, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22490708

RESUMO

OBJECTIVE: To analyze the risk factors of cognitive impairment after off-pump coronary artery bypass grafting (OPCABG). METHODS: A total of 102 patients [male: 82, age: (65.7 ± 7.1) years] undergoing OPCABG in our hospital between January 2009 and December 2010 were divided into postoperative cognitive dysfunction (POCD) group and non-POCD group by the MMSE questionnaire survey conducted at 7 days pre- and post-operation respectively. RESULTS: The incidence of POCD was 48.0% (49/102). Multivariate logistic stepwise regression analysis showed: advanced age (OR = 1.32, 95%CI: 1.10 - 1.46, P = 0.002), smoking (OR = 1.26, 95%CI: 1.18 - 1.32, P = 0.001), hypertension (OR = 1.66, 95%CI: 1.36 - 1.78, P = 0.023), diabetes (OR = 1.62, 95%CI: 1.02 - 2.84, P = 0.032), stroke (OR = 3.32, 95%CI: 1.68 - 6.49, P < 0.001), mitral regurgitation (OR = 1.48, 95%CI: 1.26 - 1.89, P < 0.001), and time of wall clamp (OR = 4.84, 95%CI: 1.08 - 7.28, P < 0.001) were independent risk factors of POCD. CONCLUSION: Advanced age, smoking, hypertension, diabetes, stroke, mitral regurgitation, and prolonged time of wall clamp are major risk factors for POCD in patients undergoing OPCABG.


Assuntos
Transtornos Cognitivos/etiologia , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Complicações Pós-Operatórias/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
20.
Ecotoxicology ; 21(5): 1281-90, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22430059

RESUMO

Bensulfuron-methyl (BSM) is a new kind of sulfonylurea herbicide widely used to control broad-leaf weeds in rice paddies. The aim of this work was to study BSM biodegradation in paddy soils with BSM-degrading bacteria Bacillus megaterium L1 and Brevibacterium sp. BH and its effect on the structures of soil bacterial community. More than 90 % of BSM could be degraded in paddy soils with 0.0355 mg kg⁻¹ BSM concentration. Addition of BSM-degrading bacterial strains Bacillus megaterium L1 into BSM contaminated paddy soil could have the half-life time of BSM compared to treatment without Bacillus megaterium L1 inoculation. Denaturing gradient gel electrophoresis and principle component analysis indicated that the diversity of the soil microbial community structure changed along with the addition of BSM, which recovered at the end of the experiment (5 weeks). Addition of BSM-degrading bacteria Bacillus megaterium L1 enriched the diversity of soil microbial community structure in paddy soils. This study provides information on the biodegradation of BSM and BSM's influences on the soil bacteria microbial community structures.


Assuntos
Bacillus megaterium/efeitos dos fármacos , Brevibacterium/efeitos dos fármacos , Herbicidas/toxicidade , Microbiologia do Solo , Poluentes do Solo/toxicidade , Compostos de Sulfonilureia/toxicidade , Bacillus megaterium/crescimento & desenvolvimento , Biodegradação Ambiental , Brevibacterium/crescimento & desenvolvimento , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Meia-Vida , Oryza , Filogenia
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